Synthesis Methodology of Nitrogen-Containing Fused Ring Compounds

Author:Zuo Zi Cong

Supervisor:wang zhi yong


Degree Year:2018





Nitrogen-containing heterocycles are an important and diverse class of structural motifs that are widely presented in the structure of natural products and drugs.It is of great significance to study the methods for the synthesis of such compounds and to develop highly efficient,economical and universal synthetic methods for studying the properties of these compounds and for further studying their biological activities and structure-activity relationships.This dissertation is divided into two parts.The first part summarizes the synthetic methodology for the construction of nitrogen-containing heterocyclic compounds.The second part mainly introduces the three methods of the synthesis of nitrogen-fused compounds.1.Iron salt promoted synthesis of indolo[2,3-b]quinolines.The 6H-indolo[2,3-b]quinolines was synthesized using ortho-aminobenzyl alcohols and indoles under the promotion of iron salt.The reaction may includes a cascade reaction of Friedel-Crafts reaction and a ring-closing reaction,which can efficiently construct the complex structure of the targeting compound in one step.In particular,when N-substituted ortho-aminobenzyl alcohols were employed as starting materials,5-substituted 5H-indolo[2,3-b]quinolines tautomer can be obtained.This method shortens the synthesis steps of such compounds and has important application.2.Iodine/tent-butyl hydroperoxide system promoted synthesis of imidazo[1,5-a]quinolines.Using simple and readily available natural amino acids and 2-methylquinoline as starting materials,under an iodine/tert-butyl hydroperoxide system,imidazo[1,5-a]quinoline compounds was synthesized.This reaction might be a tandem process.2-Methylquinoline is first oxidized into quinoline-2-carboxaldehyde under the reaction conditions.Then quinoline-2-carboxaldehyde is condensed with the amino acid.The target compound is obtained by a decarboxylation and ring-closing pathway.This method is from simple and easily obtained raw materials,and have a wide range of substrates.Especially,this reaction system is a metal-free system which meets the requirement of green chemistry.3.The synthesis of imidazo[1,5-a]quinolines under electrochemical conditions.Electrochemically assisted synthesis is a very clean methodology.Based on the previous reaction,we introduced an electrochemical synthesis method using ethyl 2-quinolineacetates as starting materials.Similar reactions was ocuured with benzylamines to obtain the imidazo[1,5-a]quinolines.The reaction yields was improved and the scope of the substrates was extended.In particular,this reaction is the first carbon-hydrogen bond amination and cyclization under the electrochemical conditions in aqueous solvents.That means a green method has been developed for the synthesis of such compounds.4.The synthesis of 2,3-dihydro-1H-quinolin-4-one and its derivatives by nano catalyst.Nano catalysts and heterogeneous catalysis often show high catalytic efficiency,low metal residue,and recyclability of the catalyst.Benzyl alcohol and o-nitroacetophenone were employed as starting materials,to synthesize 2,3-dihydro-1H-quinolin-4-one compounds in water by a hydrogen transfer strategy.Compared with the previous methods,this methodology was based on more readily available compounds and is more environmentally friendly.The main advantage of these synthetic methodologies lies in the fact that the synthesis is economy.The reactions started from cheap and easily available raw materials.The target compounds was obtained in one step through the cascade processes,and no treatment is needed during these reactions.In particular,the introduction of electrochemical synthesis avoided the usage of organic oxidants.These reactions were in line with the development direction of green chemistry.